Jarosław Dulski1,2, Catalina Cerquera-Cleves3,4, Lukasz Milanowski5,6,7, Alexa Kidd8, Emilia J Sitek1,2, Audrey Strongosky5, Ana María Vanegas Monroy9, Dennis W Dickson6, Owen A Ross6, Jolanta Pentela-Nowicka10, Jarosław Sławek1,2, Zbigniew K Wszolek5. 1. Division of Neurological and Psychiatric Nursing, Faculty of Health Sciences, Medical University of Gdansk, Gdansk, Poland. 2. Neurology Department, St Adalbert Hospital, Copernicus PL, Gdansk, Poland. 3. Neurology Unit, Pontificia Universidad Javeriana, San Ignacio Hospital, Bogotá, Colombia. 4. Movement Disorders Clinic, Clínica Universitaria Colombia, Bogotá, Colombia. 5. Department of Neurology, Mayo Clinic, Jacksonville, FL, USA. 6. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. 7. Department of Neurology, Faculty of Health Science, Medical University of Warsaw, Warsaw, Poland. 8. Clinical Genetics NZ Ltd, Christchurch, New Zealand. 9. Laboratorio Clínico Sanitas, Clinica Universitaria Colombia, Bogotá, Colombia. 10. Departement of Neurology, Medical University of Lodz, Lodz, Poland.
Abstract
BACKGROUND AND PURPOSE: Perry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP-43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease. METHODS: Data on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed. RESULTS: Parkinsonism was symmetrical, progressed rapidly and was poorly responsive to L-Dopa; nonetheless, a trial with high doses of L-Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L-Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed. There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP-43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1-related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play. CONCLUSIONS: Perry disease and other DCTN1-related diseases are increasingly diagnosed worldwide. Relatively effective symptomatic treatments are available. Further studies are needed to pave the way toward curative/gene therapy.
BACKGROUND AND PURPOSE: Perry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP-43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease. METHODS: Data on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed. RESULTS: Parkinsonism was symmetrical, progressed rapidly and was poorly responsive to L-Dopa; nonetheless, a trial with high doses of L-Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L-Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed. There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP-43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1-related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play. CONCLUSIONS: Perry disease and other DCTN1-related diseases are increasingly diagnosed worldwide. Relatively effective symptomatic treatments are available. Further studies are needed to pave the way toward curative/gene therapy.
Authors: Andre C Felicio; Katherine Dinelle; Pankaj A Agarwal; Jessamyn McKenzie; Nicole Heffernan; Jeremy D Road; Silke Appel-Cresswell; Zbigniew K Wszolek; Matthew J Farrer; Michael Schulzer; Vesna Sossi; A Jon Stoessl Journal: Mov Disord Date: 2014-05-05 Impact factor: 10.338
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